ZedScan Clinical Trials
Identification and detection of cervical disease
The ability to identify correctly those women who have and those who do not have disease is pivotal to the success of any screening programme. Prevention of cervical cancer depends on colposcopic detection and treatment of high-grade cervical intra-epithelial neoplasia (CIN 2+) in women referred with abnormal cytology.
A number of clinical studies have been completed to assess the performance of an EIS based diagnostic device in the diagnosis of cervical intraepithelial neoplasia (CIN) – Table 1.
|British Journal of Obstetrics and Gynaecology, (March, 2013)*||429|
|Gynecological Oncology, (2009)||104|
|International Journal of Gynecological Cancer, (2006)||176|
|British Journal of Obstetrics and Gynaecology, (2005)||87|
*Conclusion from pivotal multicentre trial:
Colposcopy : Key Challenges
- Reliant on visual indicators of disease
- Susceptible to Inter and intra-operator variability
- Reported sensitivity for CIN2+( HG CIN) varies between 30-99%
- Reported specificity for CIN2+ (HG-CIN) varies between 39-92%
Low colposcopic performance can result in failure to detect disease (inadequate sensitivity) or unnecessary treatment in the absence of disease (inadequate specificity).
Zilico’s multi-centre clinical trial (BJOG, 2013) has successfully demonstrated that ZedScan, when used as an adjunct to colposcopy, addresses these key challenges to deliver improvements in diagnostic accuracy.
HPV Testing as a Primary Screen
The superior sensitivity of molecular HPV testing (90%) relative to cytology (50%) is a significant driver for its consideration as a primary screening tool.
- Several studies have indicated that HPV testing is effective at finding disease within the screening population and can reduce the incidence of cervical cancer by increasing the detection and treatment of precancerous lesions missed by cytology
The predictive value of a negative test is much higher than that for cytology, providing increased confidence that disease is unlikely to develop before the subsequent round of screening and the interval between screening tests could be extended
However, HPV DNA is a marker of infection rather than disease and most infections will resolve without progression to high-grade CIN that requires treatment
- As a result the specificity of the HPV test for detection of current disease is low (50-75%) which means that the predictive value of the test is also low (17-29%)
A transition to HPV testing as the primary screen would alter the characteristics of the population referred to colposcopy.
- Although the referred population would include almost all the women at risk of developing high-grade CIN, the low specificity means that there would also be a large number of women who have an HPV infection without disease
- As a consequence the total number of patients referred to colposcopy will increase with a higher rate of false positives due to the lower specificity of HPV testing
The increased number of women referred to colposcopy, many of whom would present with new infections which are likely to clear within 5 years, will create challenges for existing patient management strategies.
A further consideration is that, whilst HPV testing would pick up women with early stage pre-cancerous lesions, this may not translate to improvements in colposcopic performance.
Porras et al 1 reported that colposcopy was poor at detecting cases of CIN2+ in HPV positive women with no acetowhite lesions present; they concluded:
“the major concern with switching from cytology to more sensitive HPV screening is management of the many HPV-positive women, including those with still nonvisible ≥CIN2 lesions. Our data support the need for a nonvisual diagnostic method to guide management and treatment of HPV-positive women.”
EIS is a non-optical diagnostic method for the diagnosis of high grade CIN, providing clinicians with increased confidence when deciding how to manage the patient, at first visit.
1Porras et al, (2012) " Switch from cytology-based to human papillomavirus test-based cervical screening: implications for colposcopy", Int. J Cancer, 130, 1879-1887
Performance of ZedScan as an adjunct to colposcopy
- Ability to detect more patients with high grade CIN
- Reduction in false positives
- Increased confidence to treat patients with disease at first visit (See & Treat/Select & Treat)